The overall objective is to delineate the nature, course, and rate of decline in memory and related functions associated with the early stages of Alzheimer's disease. Twenty patients with Alzheimer's disease associated with normal pre-morbid levels of intellectual function and forty persons with Alzheimer's disease superimposed on the severe levels of intellectual retardation associated with Down's syndrome will be studied employing delayed-matching-to-sample tests of visual, auditory, and tactile short-term retention. EEG analysis, evoked potentials, and neurological observations will be correlated with performance on the retention tests. Performance will also be compared with forty-five normal, aged, adults, twenty young patients with Down's syndrome, and two groups of twenty retarded patients without Down's syndrome to assess the role of age, diagnosis, and length of hospitalization. The data will then be related to concurrent studies of morphologic, metabolic, and electrical alterations in the brains of affected individuals and in the brains of animals with experimentally induced neurofibrillary degeneration. As post-mortem tissue become available, analysis of pathological findings can then be correlated with the accumulated clinical and behavioral observations. The work proposed will illuminate certan aspects of a neurological disease which is the primary cause of senility in the general population and which may always be associated with the mental retardation observed in aging patients with Down's syndrome. In addition, with increased understanding of the pathophysiology of the Alzheimer process upon intellectual functions, alterations noted in Down's syndrome may form the basis for hypotheses concerning possible neuronal cell defects in Down's syndrome.